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C OPYRIGHT 2014

BY

T HE J OURNAL

OF

B ONE

AND J OINT

S URGERY, I NCORPORATED

Current Concepts Review

Perioperative Blood Transfusions in

Orthopaedic Surgery
Karthikeyan E. Ponnusamy, MD, Thomas J. Kim, MD, and Harpal S. Khanuja, MD
Investigation performed at the Department of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, Maryland

Blood transfusion after orthopaedic surgery accounts for 10% of all packed red blood-cell transfusions, but use
varies substantially across hospitals and surgeons.

Transfusions can cause systemic complications, including allergic reactions, transfusion-related acute lung injury,
transfusion-associated circulatory overload, graft-versus-host disease, and infections.

Tranexamic acid is a new cost-effective blood management tool to reduce blood loss and decrease the risk of
transfusion after total joint arthroplasty.

Current clinical evidence does not justify transfusions for a hemoglobin level of >8 g/dL in the absence of symptoms.

Studies have also supported the use of this trigger in patients with a history or risk of cardiovascular disease.

Peer Review: This article was reviewed by the Editor-in-Chief and one Deputy Editor, and it underwent blinded review by two or more outside experts. The Deputy Editor
reviewed each revision of the article, and it underwent a nal review by the Editor-in-Chief prior to publication. Final corrections and clarications occurred during one or
more exchanges between the author(s) and copyeditors.

In the United States, 24 million blood components are administered annually1. Orthopaedics accounts for 10% of all
packed red blood-cell transfusions, 39% of which are used in
arthroplasty2. There are ongoing efforts to conserve blood and
decrease allogeneic transfusions for patient safety and to reduce
cost. A variety of approaches, including preoperative, intraoperative, and postoperative techniques, have been used; the
evidence for and cost-effectiveness of these techniques vary3-7.
Despite these factors, universal transfusion criteria are
lacking. Because there is no clear understanding of what level
of postoperative anemia can be tolerated, there is substantial
variation in transfusion protocols, which makes comparing
blood-preservation strategies even more difcult. Unnecessary
transfusion of packed red blood cells increases risks and costs
and wastes a scarce resource8. In this article, we discuss potential complications of transfusions to underscore the risks to

patients, address strategies to decrease the need for transfusion,

and review the orthopaedic literature to determine an acceptable level of postoperative anemia.
Transfusion Complications
Historically, blood transfusions have been associated with high
complication rates. In the early 1900s, ABO blood grouping
brought transfusions to common practice. Since then, other
blood groups, including Rh and minor antigens, have been
identied. Despite screening, however, transfusion-associated
morbidity and mortality persist (Tables I9,10 and II11-18), and incompatibilities are the second most frequent cause of transfusionassociated mortality in the U.S. 16. These complications are
reviewed to highlight the risks that are predominantly associated with allogeneic packed red blood-cell transfusions but
that can also occur with other blood components.

Disclosure: None of the authors received payments or services, either directly or indirectly (i.e., via his or her institution), from a third party in support of
any aspect of this work. One or more of the authors, or his or her institution, has had a nancial relationship, in the thirty-six months prior to submission of
this work, with an entity in the biomedical arena that could be perceived to inuence or have the potential to inuence what is written in this work. No
author has had any other relationships, or has engaged in any other activities, that could be perceived to inuence or have the potential to inuence what
is written in this work. The complete Disclosures of Potential Conicts of Interest submitted by authors are always provided with the online version of
the article.

J Bone Joint Surg Am. 2014;96:1836-44

http://dx.doi.org/10.2106/JBJS.N.00128

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TABLE I Transfusion-Associated Mortality and Morbidity Divided by Complication

Mortality (no. [%])
Complication

Morbidity (no. [%])

U.S.* (N = 198)

SHOT (N = 293)

Major (N = 1264)

Hemolytic reaction

53 (27)

24 (8.2)

110 (8.7)

897 (5.8)

Allergic reaction

12 (6)

42 (14.3)

267 (21.1)

3222 (21.0)

Transfusion-related acute lung injury

74 (37)

84 (28.7)

341 (27.0)

106 (0.7)

Transfusion-associated circulatory overload

35 (18)

20 (6.8)

92 (7.3)

151 (1.0)

2 (1)

27 (9.2)

0 (0)

0 (0)

21 (11)

29 (9.9)

97 (7.7)

12 (0.1)

Graft-versus-host disease
Infection

Minor (N = 15,357)

10

*Data are from the U.S. Food and Drug Administration cumulative reporting of transfusion-related mortalities from 2008 to 2012 . Data are
from the cumulative reports of Serious Hazards of Transfusion (SHOT), the U.K. hemovigilance system, from 2008 to 2012, for mortality and
9
major and minor morbidity .

Allergic Reaction
Allergic reactions can be caused by many factors in the transfused product, including blood components such as plasma
proteins, processing chemicals, and cytokines. Reactions to
transfused packed red blood cells (0.15% to 15%) are a common source of morbidity12.
Clinical manifestations range in severity from urticaria
to anaphylaxis. Less severe reactions are often treated with diphenhydramine, whereas more severe cases usually require corticosteroids, and anaphylaxis requires epinephrine12. There is little
evidence suggesting that pretransfusion administration of
acetaminophen and diphenhydramine prevents such reactions.
One randomized controlled trial of pretransfusion use of these
medications found no difference in transfusion reactions
but a nonsignicant decreased rate of febrile reactions with
pretreatment19.
Transfusion-Related Acute Lung Injury
Transfusion-related acute lung injury is a clinical diagnosis of
acute lung injury characteristically occurring within six hours
of a transfusion; a subset, delayed transfusion-related acute
lung injury, occurs within seventy-two hours. If other potential
etiologies coexist, the response is considered a possible transfusionrelated acute lung injury. Blood from donors who have been
pregnant multiple times20 or have had previous transfusions
presents the highest risk because of increased antibodies21. Using
only male plasma donors has decreased transfusion-related acute
lung injury rates by >60%22,23. The National Institutes of Health
Blood Bank allows AB plasma donation only from men24.
The prevalence of transfusion-related acute lung injury has
been reported to range from 0.08% to 15%, and its associated
mortality is from 5% to 10%15,17,18. Of all transfusion complications,
it is associated with the highest mortality and major morbidity1. A
randomized clinical trial showed that restrictive transfusion strategies decreased this complication from 11.4% (forty-eight of 420
patients) to 7.7% (thirty-two of 418 patients)25.
Patients can present with respiratory distress, tachycardia,
fever, hypothermia, and hypotension. Anaphylactic reactions can
be similar, but transfusion-related acute lung injury has no urti-

caria, and chest radiographs show pulmonary edema. Transfusionrelated acute lung injury is treated with supportive measures, with
70% to 90% of patients requiring mechanical ventilation18.
Transfusion-Associated Circulatory Overload
Transfusion-associated circulatory overload results in pulmonary edema from uid overload11. According to the denition
of the Public Health Agency of Canada, transfusion-associated
circulatory overload occurs within six hours after a transfusion,
but cases can occur up to twenty-four hours26. In the last decade,
the prevalence has increased, with rates reported to range from
1% to 8% for patients undergoing hip and knee arthroplasty
and from 6% to 11% for patients in the intensive care unit11,14.
The overall mortality rate has been reported to be as high as 2%
to 15%11,14-16.
Risk factors include increasing age, positive uid balance,
left ventricular dysfunction, renal dysfunction, acute myocardial
infarction, chronic pulmonary disease, acute and chronic anemia, plasma transfusion, and multiple blood product transfusions11,15. Patients at age extremes are at greatest risk: 64% of
patients who have transfusion-associated circulatory overload

TABLE II Prevalence and Mortality Rates of Transfusion

Complications
Prevalence (%)

Complication

Mortality (%)

Allergic reaction

0.15 to 15*

<1*

Transfusion-related acute
15,17,18
lung injury

0.08 to 15

5 to 10

Transfusion-associated
circulatory overload

1 to 11
13

Graft-versus-host disease

12

<1

2 to 15
84 to 100
11

*Data are from Hirayama . Data are from Alam et al. and
14
11
14
Lieberman et al. . Data are from Alam et al. , Lieberman et al. ,
15
16
Menis et al. , and a U.S. Food and Drug Administration report .
Mortality rates for severe reactions. Milder presentations are not
diagnosed, and consequently overall mortality rates are unknown.

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TABLE III Orthopaedic Studies with Data on the Odds Ratio for the Risk of Surgical Site Infection with Transfusion

Level of
Evidence

Study
34

36

Morris et. al.

35

1.96

(2003)

II

Lower extremity
oncologic

Erythema or purulent
drainage in 30 days

37

III

Internal xation of
long bone fractures

Purulent discharge or
culture positive
nonpurulent discharge

III

Adolescent idiopathic
scoliosis posterior
spinal arthrodesis

Delayed infection of >6 m

III

Thoracic and lumbar

spinal surgery

CDC criteria within 30 days

III

Lumbar spinal surgery

CDC criteria within 30 days

III

Primary total hip and

knee arthroplasty

Reoperation for suspected

infection within 3 mo of
index surgery

33

(2004)

(2010)

(2013)

39

Newman et al.

Odds Ratio

Schwarzkopf et al.
38

Y/N

CDC

(2007)

Woods et al.

SSI Criteria*

Subcapital femoral
neck fractures

Thanni and Aigoro

Ho et al.

Patient Group

II

Garcia-Alvarez et. al.

(2010)

Transfusion a Risk
Factor for SSI*

(2014)

8.02

2.85

40

*SSI = surgical site infection, and CDC = Centers for Disease Control and Prevention denition of infection . Transfusion was not found to be a
risk factor for SSI, but a volume-dependent increased odds was noted.

are seventy years or older11. Frequently seen symptoms include

dyspnea, hypoxemia, orthopnea, hypertension, tachycardia, and
congestive heart failure11,15.
The risk of this complication is reduced with pretransfusion
uid overload evaluation14, slow transfusion speed (<120 mL/hr)11,
and transfusion of a single unit11. For patients with congestive
heart failure and renal dysfunction, transfusions should be
given during dialysis. Trials support pretransfusion furosemide
usage, but ideal dosing has not been determined11,14. As opposed
to post-transfusion administration, pretransfusion use maximizes diuretic effectiveness11.
Intravenous furosemide is a rst-line treatment, after
which afterload reducers, including angiotensin-converting enzyme inhibitors, hydralazine, and nitroglycerin, are used11.
Venous Thromboembolism
Studies have suggested an increased risk of deep venous thrombosis (DVT) and pulmonary embolism with transfusion27,28. A
database study of patients with colorectal resection showed a
signicant dose-dependent increased rate of venous thromboembolism (VTE) at thirty days, with VTE developing in
1.8% (353) of 19,588 patients who had no transfusion, 3.7%
(sixty-ve) of 1751 patients who had one to two units, 4.9%
(twenty-three) of 466 patients who received three to ve units,
and 9.4% (thirteen) of 138 patients who had transfusion of six
or more units27,28. There is evidence to suggest that autologous
predonation of blood leads to fewer DVTs29,30. These studies
suggest that a combination of decreased preoperative hematocrit and depletion of other unaccounted blood proteins may
explain the decreased rate of DVTs.

Graft-Versus-Host Disease
Graft-versus-host disease presents along a spectrum of severity, with mild presentations being unrecognized and severe reactions having high mortality rates (84% to 100%)13.
In graft-versus-host disease, donor T lymphocytes proliferate
(sometimes for years), leading to immune reactions against
antigens in the recipient. Major risk factors are immunosuppression, similar donor and recipient human leukocyte antigen
haplotypes, cardiopulmonary bypass with cardiothoracic surgery, and newer blood products. Newer blood products (less than
four days from donation) and products not irradiated or leukoreduced are higher risk because T-cell survival and function
are greater.
Clinical manifestations occur two to thirty days after a
transfusion and include fever, skin blistering, diarrhea, hepatitis, and marrow aplasia. The end stage is multiorgan failure,
marrow failure, infection, and bleeding13. Management is supportive. Immunosuppressive medications are not effective, and
the effectiveness of antibiotics is unknown. Blood irradiation and
leukoreduction decrease the risk of graft-versus-host disease,
with irradiation being more effective13. U.S. blood products are
irradiated if a patient is at risk for graft-versus-host disease, a
family member donates, or cross-matching requires a strong
human leukocyte antigen similarity13.
Blood-Borne Infections
Before the recognition of human immunodeciency virus and
hepatitis, blood transfusions resulted in many new infections. Extensive screening has since been implemented to prevent transfusion
of infected blood. Per U.S. Food and Drug Administration (FDA)

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TABLE IV Orthopaedic Studies with Data on Surgical Site and Overall Infection Rates with and without Allogeneic Blood Transfusion*
Level of
Evidence

Study
42

Basora et al.
(2010)

43

Drosos et al.
(2012)

Innerhofer et al.
(2005)
Innerhofer et al.
(1999)

45

46

48

Llewelyn et al.
(2004)

49

Shander et al.
(2009)

47

Levi and Sandberg

(1998)
41

Steinitz et al.
(2001)

44

Friedman et al.
(2014)

Patient Group

SSI Criteria
40

No. of Patients

SSI Rate
(No Transfusion vs.
Transfusion) (%)

Overall Infection
Rate (No Transfusion vs.
Transfusion) (%)

6.8 vs. 6.6

NR

II

Primary TKA

CDC criteria

910

II

Primary TKA

Pyrexia and erythema,

swelling, and/or
drainage on POD 4

248

7.1 vs. 18.3; AT, 8.7

II

Primary THA and TKA

Purulent drainage and

painful erythema

286

1.0 vs. 3.0; AT, 0

II

Primary or revision
THA or TKA, spine
surgery, and pelvic
surgery

Purulent exudate

317

II

Primary or revision
THA or TKA before
and after LR

Purulent discharge

II

Primary or revision
THA or TKA, partial
hip arthroplasty,
and shoulder
arthroplasty

CDC criteria

900

NR

III

Femoral neck fractures

Culture positive or
frank pus

695

3.7 vs. 7.1

III

Primary THA

NR

1206

NR

III

Primary THA and TKA

Coded as wound
inammation or
infection

40

1477 before LR and

1436 after LR

12,177

NR

6.9 vs. 13; AT, 1.2

NR

4.7 vs. 14.8; AT, 3.5

3.6 vs. 7.1 before LR;

2.8 vs. 5.0 after LR

9.1 vs. 15 before LR;

9.4 vs. 11.9 after LR

1.7 vs. 2.4; AT, 1.3

2.0 vs. 6.1; AT, 1.2

NR
8.4 vs. 14; AT, 0#
8.0 vs. 9.9; AT, 7.3

*SSI = surgical site infection, TKA = total knee arthroplasty, THA = total hip arthroplasty, CDC = Centers for Disease Control and Prevention, NR = not reported, AT = transfused with
autologous blood, POD = postoperative day, and LR = leukoreduction. Study did not evaluate the signicance of this comparison. Signicant differences. Study included cardiac
patients, and the numbers for orthopaedic patients were separately extracted for this table. #Only eleven patients received autotransfusion.

regulations, all blood is screened for hepatitis B and C, human

immunodeciency virus, human T-lymphotrophic virus, syphilis,
West Nile virus, and Chagas disease31. However, blood products
may contain diseases not tested for such as chikungunya, malaria,
other viruses, bacteria, parasites, and prions31-33.
Immunomodulation
There is increased concern about the effects of blood transfusions on the immune system (immunomodulation). Transfusion recipients are more susceptible to pneumonia, urinary tract
infection, and surgical site infections. Irradiation, leukoreduction timing, and blood storage time may minimize these
risks.
Seven studies specic to orthopaedics have described the
odds ratio of surgical site infections with transfusion (Table III)33-40.
Five studies (two with Level-II evidence and three with LevelIII) found transfusions were associated with surgical site infection (odds ratio, 1.96 to 8.02)33-36,39; two Level-III studies found
no association37,38. Ho et al.35 found that delayed infection (six
months) after spinal arthrodesis for adolescent idiopathic scoliosis
was associated with perioperative blood transfusions. Newman
et al.39 reported that allogeneic transfusion was associated
with increased odds (odds ratio, 2.85) of reoperation for
infection within three months of primary hip and knee arthroplasty. Multiple studies found a signicant dose-dependent

increase in both surgical site and overall infections with

transfusion34,35,38,41.
Another nine studies of orthopaedic patients described
the rates of surgical site infection and/or overall postoperative
infections (urinary tract infection, pneumonia, and surgical
site infection) (Table IV)40-49. The studies generally found signicantly greater surgical site43-45,47,48 and overall infection rates
with transfusion41,44-46,48,49. Some studies showed similar rates of
infection between patients who had no transfusion and those
who received autologous units41,44-46,49, suggesting that a mechanism independent of storage may be responsible for immunomodulation. The surgical site infection rate was 1.0%
to 7.1% for patients who had no transfusion, 0% to 8.7%
for autologous transfusion, and 2.4% to 18.3% for allogeneic
transfusion42-45,47,48. The overall infection rate was 2.0% to 9.4%
for patients who had no transfusion, 0% to 7.3% for those who
had autologous transfusion, and 6.1% to 14.8% for those who
had allogeneic transfusion41,44-46,48,49.
In summary, most studies in orthopaedics have suggested
allogeneic transfusions are associated with greater infection rates.
Those studies33-38,41-49 are limited by being observational, and the
need for a transfusion may be a marker for patients prone to
infections. Although the studies adjusted for comorbidities,
other factors may have been responsible. The lower rates with
autologous transfusion warrant further investigation.

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TABLE V Strategies to Reduce the Need for Transfusion

Timing

Intervention

Studies
6

50

Preoperative

Iron therapy, intravenous erythropoietin, autologous blood

transfusion, and discontinuation of anticoagulation medicines
(aspirin and nonsteroidal anti-inammatory drugs)

Cherian et al. and Slappendel et al.

Intraoperative

Pharmacologic: brin sealants, desmopressin, thrombin, lavage

with epinephrine or norepinephrine, epsilon-aminocaproic acid,
and tranexamic acid; Nonpharmacologic: normovolemic
hemodilution, hypotensive anesthesia, tourniquets, bipolar
sealants, and cell saver

Aguilera et al. , Banerjee et al. , Cherian et al. ,

52
53
54
Chimento et al. , Gilbody et al. , Martin et al. ,
55
56
Thoms and Marwin , and Yang et al.

Postoperative

Autologous blood transfusion drains and not using drains

Jauregui et al.

Strategies to Reduce the Need for Transfusion

Multiple strategies have been developed to reduce blood loss and
the need for transfusion by intervening preoperatively, intraoperatively, and postoperatively. Other articles have reviewed
these techniques4-7 (Table V)3,4,6,7,50-56. Not all have proven to be
benecial or cost-effective. Of those listed, the available literature
favors the following: the preoperative use of erythropoietin in
certain populations and for patients who have a preoperative
hemoglobin of <10 g/dL57; the use of regional and hypotensive
anesthesia5; and the intraoperative use of tranexamic acid, which
is the most promising technique. Many recent studies have focused on its use in both local and systemic administrations and
have found decreased blood loss and transfusion rates without
evidence of signicantly increased rates of complications51-54,56.
However, those studies used various treatment dosages, timings, and formulations, and additional study is needed to
determine the most efcacious approach.
Despite these various approaches to reduce the need for
transfusion, no consensus on when to transfuse has been developed. Consequently, comparing the impact on transfusion
rates across studies is difcult. Minimizing variation in transfusions thresholds will also lead to more effective use of blood.
Transfusion Variation
On the basis of an international survey of blood utilization,
orthopaedics uses 6% to 13.8% of allogeneic and autologous
packed red blood cells: total hip arthroplasty uses 4.85%; total
knee arthroplasty, 1.93%; and other orthopaedic surgery (not
including trauma), 7.04%58. Transfusion practices vary among
clinicians and hospitals. According to one 2009 study, only 47%
(ninety-one) of 195 hospitals in the U.K. had transfusion protocols, and the rate of transfusions for total hip arthroplasty
ranged from 0% to 100%59. A 2013 study of eighty-eight U.S.
arthroplasty surgeons found differing transfusion rates: 4.8%
to 63.8% for total knee and 4.3% to 86.8% for total hip procedures60. Surgeons rationales ranged from minimizing blood use
to limiting dizziness and facilitating recovery59. Even when protocols exist, they are inconsistently applied61,62. Another study examined information from the database of the University Health
System Consortium (a large group of academic hospitals and their
afliates across the U.S.) from 2006 through 2010 and found that
transfusion rates for primary total hip arthroplasty ranged from

51

1.5% to 77.8%63. The odds ratio of receiving a transfusion at a

hospital with a high rate of transfusions compared with that at a
hospital with an average rate of transfusions was 2.4163. A study of
the U.S. Nationwide Inpatient Sample found that transfusion
rates in patients undergoing total hip arthroplasty from 2005
through 2008 had increased from 18.12% to 21.21%64. Those
investigators also found substantial variation in practice, with
hospitals in the Northeast region having an odds ratio of 1.4 of
providing a transfusion compared with all other regions64.
A systematic review of factors affecting orthopaedic transfusion decision making by Barr et al.65 found that the most common factors were low hemoglobin levels and older age. However,
the impact of other factors varied substantially, further indicating
the wide variation in practice. Hemoglobin thresholds are
often the main transfusion criteria, but the target is controversial59,65.
A survey of provider practices showed wide ranges among orthopaedists, with the trigger hemoglobin levels ranging from 6 to
11 g/dL2. Barr et al.65 found that a higher threshold was used for
a patient with symptoms of anemia (8.5 to 12 g/dL) than for
one without such symptoms (6 to 9 g/dL). Other factors predisposing to receiving a blood transfusion were lower body
weight, comorbidities (rheumatoid arthritis, history of anemia,
diabetes, cardiovascular disease, renal failure, or metastasis),
and complexity of surgery.
Clinical Studies on Restrictive Transfusion in Adults
Given this wide variety in practices, assessment of the rationale
and evidence for transfusion is warranted to avoid unnecessary
risk. Packed red blood cells are given for concerns of decreased
oxygen delivery. However, the decreased viscosity of anemic
blood can compensate with greater blood ow. Research indicates no clinically relevant difference in oxygen delivery for
hemoglobin levels from 6 to 10 g/dL1. In studies of Jehovahs
Witness patients66,67, the risk of morbidity and mortality increased only for a hemoglobin level of <7 g/dL. Goodnough
et al.1 suggested that cardiovascular disease or older age warrants a higher target.
Randomized controlled trials of patients in critical care,
after cardiothoracic surgery, and with gastrointestinal bleeding
found similar to better mortality and morbidity outcomes
with restrictive (a hemoglobin level of 7 to 8 g/dL) compared
with liberal (a hemoglobin level of 9 to 10 g/dL) transfusion

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protocols25,68,69. A Cochrane review of medical and surgical populations noted that, compared with liberal transfusion protocols,
restrictive protocols resulted in similar complication rates, signicantly lower in-hospital mortality, similar thirty-day mortality, and comparable duration of stay and function assessed
by ambulatory status and fatigue questionnaires70. Those authors concluded that restrictive thresholds can be used for most
patients, even those with a history of cardiovascular disease70.
A systematic review of the literature identied seven studies
involving orthopaedic patients that used restrictive protocols (see
Appendix)71-77. The largest study, a randomized controlled trial of
patients who were surgically treated for a hip fracture by Carson
et al.72, had approximately 1000 patients per group. The authors
conducted a pilot study of eighty-four patients with hemoglobin
levels of <10 g/dL in the rst three postoperative days71. The patients were randomized to a liberal (10 g/dL) or restrictive (8 g/dL
or symptoms of anemia) transfusion group. There was no difference in ability to walk 10 ft (3 m) or in mortality rates at sixty
days. No signicant difference was found in outcome between
these groups or in the subgroup of patients with cardiovascular
disease71. Using these results, a larger study (2000 patients) was
powered to 90% to detect an absolute 8% intergroup difference72.
The inclusion criteria were rened to only patients with history
of, or risk factors for, cardiovascular disease. Despite this sicker
population, no signicant difference was found in the primary
outcome of mortality and inability to walk. No signicant differences were found with respect to mortality rates at thirty and sixty
days, complications, duration of stay, functional activity, surgical
site infection, or DVT and pulmonary embolism. The restrictive
transfusion protocol used only one-third the number of packed
red blood-cell units used by the liberal protocol72.
Another randomized controlled trial of 120 patients with
a hip fracture focused on the ability to walk, comparing liberal
(10 g/dL) and restrictive (8 g/dL) transfusion thresholds73.
Despite randomization, the two groups had different baseline
characteristics: the restrictive group had higher American Society
of Anesthesiologists scores and number of screw xations,
whereas the liberal group had more sliding hip screws and
intramedullary devices. No difference was found in functional
outcome (walking ability, duration of stay, and number of patients achieving independent walking) except for patient-reported
fatigue scores on postoperative day 2. However, the restrictive
group had signicantly more cardiovascular complications (10%
versus 2%) and thirty-day mortality (8% versus 0%).
Other studies have evaluated patients who had total hip
and knee arthroplasties74-77. Three of the studies were limited by
inconsistent baseline comparison protocol75-77 and variations
at different test sites for a multisite trial76,77. In fact, one of
the studies77 found a 39% increase in the transfusion rate with
the new so-called restrictive protocol at one of the study sites.
Consequently, these researchers performed a post hoc analysis
of their data by switching the patient classication in that
hospital such that the new protocol was considered liberal
because it was less restrictive than the established protocol.
Patient classication in the other hospitals remained the same.
With this recategorization, they found that the restrictive group

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TABLE VI Grades of Recommendation for Summaries or Reviews

of Orthopaedic Surgical Studies*
Recommendation

Grade of Evidence*

Limit transfusion of allogeneic packed

red blood cells to patients who have
a hemoglobin level of <8 g/dL or
symptomatic anemia.

Avoid transfusion of allogeneic packed

red blood cells because it can increase
the risk of infection.

Avoid transfusion of packed red blood

cells because it can increase deep
venous thrombosis and pulmonary
embolism rates.

*Grade A indicates good evidence (Level-I studies with consistent

ndings) for or against recommending the intervention; Grade B,
fair evidence (Level-II or III studies with consistent ndings) for or
against recommending the intervention; Grade C, conicting or
poor-quality evidence (Level-IV or V studies) not allowing a recommendation for or against the intervention; and Grade I, there is
78
insufcient evidence to make a recommendation .

had signicantly reduced blood usage (26.4% versus 39.1%)

and signicantly lower infection rates (5.4% versus 10.2%),
specically urinary tract infections (8% versus 12%) and surgical site infection (2% versus 9%). Similar to the study by
Carson et al.72, no difference was detected in functional outcomes measured, that is, quality of life and fatigue76.
Grover et al.74 focused on identifying silent myocardial
ischemia in patients with total knee and hip arthroplasties with
protocols similar to those in the study by Carson et al.72. Patients more than fty-ve years old were monitored from
twelve hours before until three days after surgery to identify
electrocardiographic changes. Patients with certain cardiovascular history were excluded because of the difculty of identifying electrocardiographic changes. There was no difference
in the number of silent ischemic events, but when ischemic, the
liberal group had a signicantly greater ischemic load (minutes
of ischemia on a Holter monitor divided by total monitoring
time). Sufcient power was lacking for conclusive evidence. No
differences in duration of stay or complications were found74.
Many studies are severely limited compared with the
study by Carson et al.72 because they did not restrict patient
enrollment to those who would denitely receive a transfusion
in the liberal protocol. The other studies contained, in both
groups, patients with a hemoglobin level of >10 g/dL who
would not receive a transfusion under either protocol. Additionally, multiple studies are hindered by inconsistent preintervention
protocols75-77.
Overall, Grade-A evidence78 supports using a restrictive
hemoglobin transfusion trigger of 8 g/dL or symptomatic
anemia for patients with or without a history of cardiovascular
disease because there is no impact on cardiovascular complications, rehabilitation, or duration of stay (Table VI). Grade-B
evidence78 suggests that transfusions increase infection rates. In

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their review, Carson et al.70 found a nonsignicant 19% decrease in

infection rates with restrictive protocols. Grade-I evidence78 supports the association between transfusions and VTEs.
Slappendel et al.50 conducted an analysis of their database
of information on orthopaedic patients and standardized their
perioperative management to minimize blood transfusions. Their
interventions included iron and/or erythropoietin pretreatment for certain patients, stopping aspirin and nonsteroidal antiinammatories, perioperative normothermia, postoperative
blood salvage, use of aprotinin (aprotinin is no longer approved
in the U.S., and this study was conducted before the introduction
of tranexamic acid), and consistent use of a restrictive transfusion
trigger. They found that the transfusion rate was reduced from
34% to 7% and the rate of deep wound infections from 2.6% to
1.5%50. Their report showed that implementation of a consistent
transfusion protocol leads to improved results, and current data
on various transfusion interventions should be used in constructing an institutions protocol.
Transfusion of packed red blood cells has multiple associated complications and may place patients at greater risk
for infections, including surgical site infections. Although there
are many techniques for minimizing the need for a transfusion,
there is substantial variation in transfusion practices with no
universally accepted protocol at the present time. Current
evidence suggests that a restrictive protocol (a hemoglobin

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level of <8 g/dL) is not detrimental to patient outcomes and

can decrease the risk of infection and cost. More conservative
transfusion protocols should be adopted and integrated with
the use of blood preservation techniques in a standardized
fashion, similar to the work of Slappendel et al.50. Such
standardization and critical review of practices will more efciently use blood products, protect patients, and decrease costs.
Appendix
A table showing data on restrictive transfusion threshold
studies in orthopaedics is available with the online version of this article as a data supplement at jbjs.org. n

Karthikeyan E. Ponnusamy, MD
Thomas J. Kim, MD
Harpal S. Khanuja, MD
c/o Elaine P. Henze, BJ, ELS,
Medical Editor and Director,
Editorial Services,
Department of Orthopaedic Surgery,
The Johns Hopkins University/Johns Hopkins Bayview Medical Center,
4940 Eastern Avenue, #A665,
Baltimore, MD 21224-2780.
E-mail address: ehenze1@jhmi.edu

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